TMC (Topotecan, Cyclophosphamide and Melphalan) for Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01039025
Recruitment Status : Completed
First Posted : December 24, 2009
Last Update Posted : August 1, 2012
SmithKline Beecham
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
To determine the efficacy of high-dose topotecan, cyclophosphamide and melphalan in patients with Multiple Myeloma.

Condition or disease Intervention/treatment Phase
Myeloma Drug: Topotecan Drug: Cyclophosphamide Drug: Melphalan Other: Peripheral Blood Stem Cells Phase 2

Detailed Description:

Patients in this study will have a catheter (a tube) placed in the vein below the collarbone. Most of the drugs used in the study will be given through the catheter. Blood stem cells will be collected through this tube also.

Before treatment starts, patients will have a complete physical exam, including blood and urine tests. A dentist will perform a dental exam either at M.D. Anderson or elsewhere. A chest x-ray and bone x-rays will be done. An EKG and a heart scan will be done to test heart function. A breathing test will be done. Patients will also be screened for HIV and Hepatitis.

Blood stem cells will be collected from patients when white blood cell counts are normal. This will be after earlier chemotherapy or after a bone marrow growth factor (G-CSF) has been given. Collecting stem cells takes about 3 hours. It takes from 1 to 6 sessions to get the needed amount of cells. The process is called apheresis. A machine is attached to the catheter, and blood is drawn. The machine removes the stem cells from the blood and the blood is then returned to the body through the catheter. G-CSF is injected under the skin twice a day during the time the stem cells are collected. The stem cells are stored frozen and will be used later to help patients recover from the high-dose chemotherapy.

After stem cells are collected, patients will receive high-dose chemotherapy. Cyclophosphamide is given over 2 hours on Days 1 - 3. Melphalan is given on Days 4 and 5. Topotecan is given over 30 minutes on Days 1 - 5, right after cyclophosphamide or melphalan. On Day 6, no drugs are given. On Day 7, some or all of the stem cells will be reinfused. G-CSF will be given once a day until blood counts return to normal.

Patients must stay in the hospital for the high-dose drug treatment. The length of stay will be about 3 weeks. Blood tests will be done daily while in hospital, then once a week for the first month. A bone marrow sample will be taken on Day 30. Blood samples will be taken 4 times in the first year and once a year after that. Thyroid gland tests and a bone marrow test will be done once a year.

This is an investigational study. Cyclophosphamide, melphalan, and topotecan are approved by the FDA. Their use together in this study is experimental. All participants will be enrolled at UTMDACC.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of High-Dose Topotecan, Cyclophosphamide and Melphalan for the Treatment of Multiple Myeloma
Study Start Date : February 2002
Actual Primary Completion Date : May 2006
Actual Study Completion Date : May 2006

Arm Intervention/treatment
Experimental: TMC
Topotecan, Melphalan, and Cyclophosphamide
Drug: Topotecan
After stem cells are collected, Topotecan 3.5 mg/m^2 intravenously given over 30 minutes on Days 1 - 5.
Other Name: Hycamtin
Drug: Cyclophosphamide
After stem cells are collected, Cyclophosphamide 1 g/m^2/day intravenously given over 2 hours on Days 1 - 3.
Other Names:
  • Cytoxan
  • Neosar
Drug: Melphalan
After stem cells are collected, Melphalan 70 mg/m^2/day intravenously given on Days 4 and 5.
Other Name: Alkeran
Other: Peripheral Blood Stem Cells
On Day 7, some or all of the stem cells will be reinfused.

Primary Outcome Measures :
  1. Response Rate [ Time Frame: Within 180 days after treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with intermediate or high tumor mass multiple myeloma with responsive or primary refractory disease; and patients with responsive or refractory relapse.
  2. Physiological age </= 70.
  3. Zubrod performance status < 3.
  4. Life expectancy greater than 12 weeks.
  5. Left ventricular ejection fraction >/= 50%.
  6. No uncontrolled arrythmias or symptomatic cardiac disease.
  7. FEV1, FVC and DLCO >/= 50%.
  8. No symptomatic pulmonary disease.
  9. Serum creatinine < 1.5 mg/dL.
  10. Serum bilirubin < 2x upper limit of normal.
  11. No evidence of chronic or active hepatitis or cirrhosis.
  12. Patient is not pregnant.
  13. Patients or guardian able to sign informed consent.
  14. No active CNS disease.
  15. Platelet count > 100K.

Exclusion Criteria:

1) N/A

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01039025

United States, Texas
U.T. M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
SmithKline Beecham
Principal Investigator: Michelle Donato, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01039025     History of Changes
Other Study ID Numbers: DM01-331
First Posted: December 24, 2009    Key Record Dates
Last Update Posted: August 1, 2012
Last Verified: July 2012

Keywords provided by M.D. Anderson Cancer Center:
Stem Cell Harvest
Peripheral Blood Stem Cells

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors